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"Sadakane, Atsuko"
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Radiation risk of central nervous system tumors in the Life Span Study of atomic bomb survivors, 1958–2009
by
Preston, Dale L.
,
Sakata, Ritsu
,
Ozasa, Kotaro
in
Adult
,
Atomic Bomb Survivors - statistics & numerical data
,
Atomic bombs
2020
Radiation exposure is among the few factors known to be associated with risk of central nervous system (CNS) tumors. However, the patterns of radiation risk by histological type, sex or age are unclear. We evaluated radiation risks of first primary glioma, meningioma, schwannoma, and other or not otherwise specified (other/NOS) tumors in the Life Span Study cohort of atomic bomb survivors. Cases diagnosed between 1958 and 2009 were ascertained through population-based cancer registries in Hiroshima and Nagasaki. To estimate excess relative risk per Gy (ERR/Gy), we fit rate models using Poisson regression methods. There were 285 CNS tumors (67 gliomas, 107 meningiomas, 49 schwannomas, and 64 other/NOS tumors) among 105,444 individuals with radiation dose estimates to the brain contributing 3.1 million person-years of observation. Based on a simple linear model without effect modification, ERR/Gy was 1.67 (95% confidence interval, CI: 0.12 to 5.26) for glioma, 1.82 (95% CI: 0.51 to 4.30) for meningioma, 1.45 (95% CI: − 0.01 to 4.97) for schwannoma, and 1.40 (95% CI: 0.61 to 2.57) for all CNS tumors as a group. For each tumor type, the dose–response was consistent with linearity and appeared to be stronger among males than among females, particularly for meningioma (
P
= 0.045). There was also evidence that the ERR/Gy for schwannoma decreased with attained age (
P
= 0.002). More than 60 years after the bombings, radiation risks for CNS tumors continue to be elevated. Further follow-up is necessary to characterize the lifetime risks of specific CNS tumors following radiation exposure.
Journal Article
Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958–2009
2017
This is the third analysis of solid cancer incidence among the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki, adding eleven years of follow-up data since the previously reported analysis. For this analysis, several changes and improvements were implemented, including updated dose estimates (DS02R1) and adjustment for smoking. Here, we focus on all solid cancers in aggregate. The eligible cohort included 105,444 subjects who were alive and had no known history of cancer at the start of follow-up. A total of 80,205 subjects had individual dose estimates and 25,239 were not in either city at the time of the bombings. The follow-up period was 1958–2009, providing 3,079,484 person-years of follow-up. Cases were identified by linkage with population-based Hiroshima and Nagasaki Cancer Registries. Poisson regression methods were used to elucidate the nature of the radiation-associated risks per Gy of weighted absorbed colon dose using both excess relative risk (ERR) and excess absolute risk (EAR) models adjusted for smoking. Risk estimates were reported for a person exposed at age 30 years with attained age of 70 years. In this study, 22,538 incident first primary solid cancer cases were identified, of which 992 were associated with radiation exposure. There were 5,918 cases (26%) that occurred in the 11 years (1999–2009) since the previously reported study. For females, the dose response was consistent with linearity with an estimated ERR of 0.64 per Gy (95% CI: 0.52 to 0.77). For males, significant upward curvature over the full dose range as well as restricted dose ranges was observed and therefore, a linear-quadratic model was used, which resulted in an ERR of 0.20 (95% CI: 0.12 to 0.28) at 1 Gy and an ERR of 0.010 (95% CI: −0.0003 to 0.021) at 0.1 Gy. The shape of the ERR dose response was significantly different among males and females (P = 0.02). While there was a significant decrease in the ERR with increasing attained age, this decrease was more rapid in males compared to females. The lowest dose range that showed a statistically significant dose response using the sex-averaged, linear ERR model was 0–100 mGy (P = 0.038). In conclusion, this analysis demonstrates that solid cancer risks remain elevated more than 60 years after exposure. Sex-averaged upward curvature was observed in the dose response independent of adjustment for smoking. Findings from the current analysis regarding the dose-response shape were not fully consistent with those previously reported, raising unresolved questions. At this time, uncertainties in the shape of the dose response preclude definitive conclusions to confidently guide radiation protection policies. Upcoming results from a series of analyses focusing on the radiation risks for specific organs or organ families, as well as continued follow-up are needed to fully understand the nature of radiation-related cancer risk and its public health significance. Data and analysis scripts are available for download at: http://www.rerf.or.jp.
Journal Article
Epidemiologic Features of Kawasaki Disease in Japan: Results of the 2009-2010 Nationwide Survey
by
Uehara, Ritei
,
Aoyama, Yasuko
,
Tsuboi, Satoshi
in
Aneurysms
,
Cardiovascular disease
,
Epidemiology
2012
Background: Although the number of patients and incidence rate of Kawasaki disease (KD) are increasing in Japan, the most recent epidemiologic features of KD are not known. Methods: The 21st nationwide survey of KD was conducted in 2011 and included patients treated for the disease in 2009 and 2010. Hospitals specializing in pediatrics, and hospitals with a total of 100 or more beds and a pediatric department, were asked to report all patients with KD during the 2 survey years. Results: A total of 1445 departments and hospitals reported 23 730 KD patients (10 975 in 2009 and 12 755 in 2010): 13 515 boys and 10 215 girls. The annual incidence rates were 206.2 and 239.6 per 100 000 children aged 0 to 4 years in 2009 and 2010, respectively; the 2010 rate was the highest ever reported in Japan. Monthly number of patients peaked during winter to spring months; lower peaks were noted during summer months. However, the seasonal patterns in 2009 and 2010 differed from those of previous years. The age-specific incidence rate had a monomodal distribution, with a peak during the latter half of the year of birth. The prevalences of cardiac lesions during acute KD and cardiac sequelae were higher among infants and older age groups. Despite a decrease in prevalence, the proportion of patients with giant coronary aneurysms--the most severe sequela of KD--did not substantially decrease. Conclusions: The incidence rate and number of patients with KD continue to increase in Japan. [PUBLICATION ABSTRACT]
Journal Article
Incidence of Breast Cancer in the Life Span Study of Atomic Bomb Survivors: 1958–2009
2018
The importance of reproductive history in breast tissue development and etiology of sporadic breast cancer in females is well established. However, there is limited evidence of factors, other than age, that modify risk of radiation-related breast cancer. In this study, we evaluated breast cancer incidence in the Life Span Study cohort of atomic bomb survivors, adding 11 years of follow-up and incorporating reproductive history data. We used Poisson regression models to describe radiation risks and modifying effects of age and reproductive factors. Among 62,534 females, we identified 1,470 breast cancers between 1958 and 2009. Of 397 new cases diagnosed since 1998, 75% were exposed before age 20. We found a strong linear dose response with excess relative risk (ERR) of 1.12 per Gy [95% confidence interval (CI): 0.73 to 1.59] for females at age 70 after exposure at age 30. The ERR decreased with increasing attained age (P = 0.007) while excess absolute rate (EAR) increased with attained age up to age 70 (P < 0.001). Age at menarche was a strong modifier of the radiation effect: for a given dose, both the ERR and EAR decreased with increasing age at menarche (P = 0.007 and P < 0.001). Also, independently, age-at-exposure effects on ERR and EAR differed before and after menarche (P = 0.043 and P = 0.015, respectively, relative to log-linear trends), with highest risks for exposures around menarche. Despite the small number of male breast cancers (n = 10), the data continue to suggest a dose response (ERR per Gy = 5.7; 95% CI: 0.3 to 30.8; P = 0.018). Persistently increased risk of female breast cancer after radiation exposure and its modification pattern suggests heightened breast sensitivity during puberty.
Journal Article
Risk of death among children of atomic bomb survivors after 62 years of follow-up: a cohort study
2015
No clear epidemiological hereditary effects of radiation exposure in human beings have been reported. However, no previous studies have investigated mortality into middle age in a population whose parents were exposed to substantial amounts of radiation before conception. We assessed mortality in children of the atomic bomb survivors after 62 years of follow-up.
In this prospective cohort study, we assessed 75 327 singleton children of atomic bomb survivors in Hiroshima and Nagasaki and unexposed controls, born between 1946 and 1984, and followed up to Dec 31, 2009. Parental gonadal doses of radiation from the atomic bombings were the primary exposures. The primary endpoint was death due to cancer or non-cancer disease, based on death certificates.
Median follow-up was 54·3 years (IQR 45·4–59·3). 5183 participants died from disease. The mean age of the 68 689 surviving children at the end of follow-up was 53·1 years (SD 7·9) with 15 623 (23%) older than age 60 years. For parents who were exposed to a non-zero gonadal dose of radiation, the mean dose was 264 mGy (SD 463). We detected no association between maternal gonadal radiation exposure and risk of death caused by cancer (hazard ratio [HR] for 1 Gy change in exposure 0·891 [95% CI 0·693–1·145]; p=0·36) or risk of death caused by non-cancer diseases (0·973 [0·849–1·115]; p=0·69). Likewise, paternal exposure had no effect on deaths caused by cancer (0·815 [0·614–1·083]; p=0·14) or deaths caused by non-cancer disease (1·103 [0·979–1·241]; p=0·12). Age or time between parental exposure and delivery had no effect on risk of death.
Late effects of ionising radiation exposure include increased mortality risks, and models of the transgenerational effects of radiation exposure predict more genetic disease in the children of people exposed to radiation. However, children of people exposed to the atomic bombs in Hiroshima and Nagasaki had no indications of deleterious health effects after 62 years. Epidemiological studies complemented by sensitive molecular techniques are needed to understand the overall effects of preconception exposure to ionising radiation on human beings.
Japanese Ministry of Health, Labour and Welfare, US Department of Energy.
Journal Article
Body-Mass Index and Pancreatic Cancer Incidence: A Pooled Analysis of Nine Population-Based Cohort Studies With More Than 340,000 Japanese Subjects
2018
Background: A high body mass index (BMI) has been proposed as an important risk factor for pancreatic cancer. However, this association of BMI with pancreatic cancer risk has not been confirmed in Asian populations. Methods: We evaluated the association between BMI (either at baseline or during early adulthood) and pancreatic cancer risk by conducting a pooled analysis of nine population-based prospective cohort studies in Japan with more than 340,000 subjects. Summary hazard ratios (HRs) were estimated by pooling study-specific HRs for unified BMI categories with a random-effects model. Results: Among Japanese men, being obese at baseline was associated with a higher risk of pancreatic cancer incidence (≥30 kg/m2 compared with 23 to <25 kg/m2, adjusted HR 1.71; 95% confidence interval [CI], 1.03–2.86). A J-shaped association between BMI during early adulthood and pancreatic cancer incidence was seen in men. In contrast, we observed no clear association among women, although there may be a positive linear association between BMI at baseline and the risk of pancreatic cancer (per 1 kg/m2, adjusted HR 1.02; 95% CI, 1.00–1.05). Conclusions: Pooling of data from cohort studies with a considerable number of Japanese subjects revealed a significant positive association between obesity and pancreatic cancer risk among men. This information indicates that strategies that effectively prevent obesity among men might lead to a reduced burden of pancreatic cancer, especially in Asian populations.
Journal Article
Radiation-Related Risk of Cancers of the Upper Digestive Tract among Japanese Atomic Bomb Survivors
2019
As a follow-up to the comprehensive work on solid cancer incidence in the Life Span Study (LSS) cohort of atomic bomb survivors between 1958 and 1998, we report here on updated radiation risk estimates for upper digestive tract cancers. In this study, we added 11 years of follow-up (1958–2009), used improved radiation dose estimates, considered effects of smoking and alcohol consumption and performed dose-response analyses by anatomical sub-site. In examining 52 years'worth of data, we ascertained the occurrence of 394 oral cavity/pharyngeal cancers, 486 esophageal cancers and 5,661 stomach cancers among 105,444 subjects. The radiation risk for oral cavity/pharyngeal cancer, other than salivary gland, was elevated but not significantly so. In contrast, salivary gland cancer exhibited a strong linear dose response with excess relative risk (ERR) of 2.54 per Gy [95% confidence interval (CI): 0.69 to 6.1]. Radiation risk decreased considerably with increasing age at time of exposure (–66% per decade, 95% CI: –88% to –32%). The dose response for esophageal cancer was statistically significant under a simple linear, linear-quadratic and quadratic model. Both linear-quadratic and quadratic models described the data better than a simple linear model and, of the two, the quadratic model showed a marginally better fit based on the Akaike Information Criteria. Sex difference in linear ERRs was not statistically significant; however, when the dose-response shape was allowed to vary by sex, statistically significant curvature was found among males, with no evidence of quadratic departure from linearity among females. The risk for stomach cancer increased significantly with dose and there was little evidence for quadratic departure from linearity among either males or females. The sex-averaged ERR at age 70 was 0.33 per Gy (95% CI: 0.20 to 0.47). The ERR decreased significantly (–1.93 power of attained age, 95% CI: –2.94 to –0.82) with increasing attained age, but not with age at exposure, and was higher in females than males (P = 0.02). Our results are largely consistent with the results of prior LSS analyses. Salivary gland, esophageal and stomach cancers continue to show significant increases in risk with radiation dose. Adjustment for lifestyle factors had almost no impact on the radiation effect estimates. Further follow-up of the LSS cohort is important to clarify the nature of radiation effects for upper digestive tract cancers, especially for oral cavity/pharyngeal and esophageal cancers, for which detailed investigation for dose-response shape could not be conducted due to the small number of cases.
Journal Article
Epidemiologic Features of Kawasaki Disease in Japan: Results of the 2007–2008 Nationwide Survey
by
Uehara, Ritei
,
Aoyama, Yasuko
,
Chihara, Izumi
in
Autoimmune diseases
,
Cardiovascular Disease
,
Epidemiology
2010
Background: The most recent epidemiologic features of Kawasaki disease (KD) are unknown. Methods: The 20th nationwide survey of KD was conducted in 2009, and included patients treated for the disease in 2007 and 2008. Hospitals specializing in pediatrics, and hospitals with pediatric departments and 100 or more beds, were asked to report all patients with KD during the 2 survey years. Results: From a total of 1540 departments and hospitals, 23 337 patients (11 581 in 2007 and 11 756 in 2008) were reported: 13 523 boys and 9814 girls. The annual incidence rates were 215.3 and 218.6 per 100 000 children aged 0-4 years in 2007 and 2008, respectively. These were the highest annual KD incidence rates ever recorded in Japan. The monthly number of patients peaked during the winter months; smaller increases were noted in the summer months. The age-specific incidence rate showed a monomodal distribution with a peak at age 9-11 months. The prevalences of both cardiac lesions during the acute phase of the disease and cardiac sequelae were higher among infants and older age groups. Conclusions: The incidence rate and number of patients with KD in Japan continue to increase. [PUBLICATION ABSTRACT]
Journal Article
Meat subtypes and colorectal cancer risk: A pooled analysis of 6 cohort studies in Japan
by
Akter, Shamima
,
Tsugane, Shoichiro
,
Nagata, Chisato
in
Animals
,
Asian Continental Ancestry Group
,
Beef
2019
Red meat and processed meat have been suggested to increase risk of colorectal cancer (CRC), especially colon cancer. However, it remains unclear whether these associations differ according to meat subtypes or colon subsites. The present study addressed this issue by undertaking a pooled analysis of large population‐based cohort studies in Japan: 5 studies comprising 232 403 participants (5694 CRC cases) for analysis based on frequency of meat intake, and 2 studies comprising 123 635 participants (3550 CRC cases) for analysis based on intake quantity. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model and then pooled using the random effect model. Comparing the highest vs lowest quartile, beef intake was associated with an increased risk of colon cancer in women (pooled HR 1.20; 95% CI, 1.01‐1.44) and distal colon cancer (DCC) risk in men (pooled HR 1.30; 95% CI, 1.05‐1.61). Frequent intake of pork was associated with an increased risk of distal colon cancer in women (pooled HR 1.44; 95% CI, 1.10‐1.87) for “3 times/wk or more” vs “less than 1 time/wk”. Frequent intake of processed red meat was associated with an increased risk of colon cancer in women (pooled HR 1.39; 95% CI, 0.97‐2.00; P trend = .04) for “almost every day” vs “less than 1 time/wk”. No association was observed for chicken consumption. The present findings support that intake of beef, pork (women only), and processed red meat (women only) might be associated with a higher risk of colon (distal colon) cancer in Japanese. As shown in figure A and figure B, comparing the highest versus lowest quartile, beef intake was associated with an increased risk of colon cancer in women (pooled HR 1.20, 95% CI 1.01‐1.44) and distal colon cancer (DCC) risk in men (pooled HR 1.30, 95% CI 1.05‐1.61). Figure C shows that frequent intake of pork was associated with an increased risk of DCC in women (pooled HR 1.44, 95% CI 1.10‐1.87) for “3 times/week or more” versus “<1time/week”. Figure D shows that frequent intake of processed red meat was associated with an increased risk of colon cancer in women (pooled HR 1.39, 95% CI 0.97‐2.00; p‐trend=0.04) for “almost every day” versus “<1 time/week”.
Journal Article
Radiation and Risk of Liver, Biliary Tract, and Pancreatic Cancers among Atomic Bomb Survivors in Hiroshima and Nagasaki: 1958–2009
2019
The Life Span Study (LSS) of atomic bomb survivors has consistently demonstrated significant excess radiation-related risks of liver cancer since the first cancer incidence report. Here, we present updated information on radiation risks of liver, biliary tract and pancreatic cancers based on 11 additional years of follow-up since the last report, from 1958 to 2009. The current analyses used improved individual radiation doses and accounted for the effects of alcohol consumption, smoking and body mass index. The study participants included 105,444 LSS participants with known individual radiation dose and no known history of cancer at the start of follow-up. Cases were the first primary incident cancers of the liver (including intrahepatic bile duct), biliary tract (gallbladder and other and unspecified parts of biliary tract) or pancreas identified through linkage with population-based cancer registries in Hiroshima and Nagasaki. Poisson regression methods were used to estimate excess relative risks (ERRs) and excess absolute risks (EARs) associated with DS02R1 doses for liver (liver and biliary tract cancers) or pancreas (pancreatic cancer). We identified 2,016 incident liver cancer cases during the follow-up period. Radiation dose was significantly associated with liver cancer risk (ERR per Gy: 0.53, 95% CI: 0.23 to 0.89; EAR per 10,000 person-year Gy: 5.32, 95% CI: 2.49 to 8.51). There was no evidence for curvature in the radiation dose response (P=0.344). ERRs by age-at-exposure categories were significantly increased among those who were exposed at 0–9, 10–19 and 20–29 years, but not significantly increased after age 30 years, although there was no statistical evidence of heterogeneity in these ERRs (P = 0.378). The radiation ERRs were not affected by adjustment for smoking, alcohol consumption or body mass index. As in previously reported studies, radiation dose was not associated with risk of biliary tract cancer (ERR per Gy: –0.02, 95% CI: –0.25 to 0.30). Radiation dose was associated with a nonsignificant increase in pancreatic cancer risk (ERR per Gy: 0.38, 95% CI: <0 to 0.83). The increased risk was statistically significant among women (ERR per Gy: 0.70, 95% CI: 0.12 to 1.45), but not among men.
Journal Article